The MCSDA candidate is a Veterinary Neurologist interested in developing and applying NMR methods to study animal models of human neurodegenerative diseases. The candidates long-term goal is a career in biomedical research studying the pathophysiology and therapy of neurodegeneration in animal models of human disease using magnetic resonance imaging (MRI magnetization transfer imaging ((MTI) and magnetic resonance spectroscopy (MRS). A career development plan including coursework in MR physics and medical genetics, consistent interaction with the Metabolic Magnetic Resonance Research Computer Center, as well as a Research Plan with specific and testable hypotheses will provide the candidate with the training necessary to achieve scientific independence in the study of neurodegeneration. The Veterinary School of the University pf Pennsylvania and my mentor, Dr. Jerry Glickson, of the Medical School of the University of Pennsylvania, have enthusiastically pledged their support for the next three years of training. This application concerns the study of canine and murine animal models of lysosomal storage disorders: mucopolysaccharidosis (MPS) VII and globoid-cell leukodystrophy (GCL). Lysosomal storage disorders affect approximately 1/1500 humans and no effective therapy has yet been developed for those patients with central nervous system manifestations of disease. The effectiveness of bone marrow transplantation and neural progenitor cell transplantation in canine and murine models of these diseases has yielded promising data regarding the treatment of neurodegeneration. Indeed, bone marrow transplantation to treat these disorders in human patients is currently being pursued based on the success demonstrated in animal models. MRI, MTI, and MRS offer exciting potential for increased tissue characterization and can be used to determine, in vivo, whether neurodegeneration is progressing, has ceased to progress, or is regressing following therapy. Specifically, animal MR scanners will be used to collect MRI, MTI, and MRS data in order to compare volumetric data and the concentrations of specific MR detectable metabolites between affected and treated animals. The "gold standard" for the efficacy of treatment will be post mortem tissue anal analysis for enzyme and substrate activity. These post mortem data will be compared to volumetric data and to the concentrations of MR detectable metabolites in order to identify MR data which are highly correlated with effective therapy.